From pest-resistant corn to creepy glowing fish, genetically engineered organisms are creeping into our lives. But most of today's GMOs vary marginally from the original animal or plant—there is an addition or deletion of a couple genes, which is like adding or scrubbing a line from Hamlet and calling it a new play. But a team of geneticists led by Jef Boeke at Johns Hopkins University is dreaming much, much bigger.

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The team is genetically engineering an entire organism—a yeast—from scratch, as part of the Synthetic Yeast 2.0 project. They have designed and written a code made up of roughly 11 million letters of DNA—the As, Cs, Gs, and Ts that write the book of life—which they are synthesizing and subbing in for a yeast's natural DNA. To integrate their new chromosome, the researchers used the organism's natural affinity for uptaking segments of DNA, slowly introducing chunks of it into a living yeast in an 11-part process. And as they reported today in the journal Science, their project is progressing splendidly. They have just finished their first phase, building and integrating an entire chromosome.

"Yeasts have 16 chromosomes, and we've just completed chromosome 3," Boeke says. "Now it's just a matter of money and time."

Yeasts are one of nature's great decomposers, found worldwide on places like rotting plants. They can ferment sugars into alcohol and bubbly carbon dioxide, and their importance in modern society can't be understated. Your insulin injection, biofuel in your car—even your cold pint of beer owes its existence to these microbial alchemists. Finding ways to hack in and build synthetic yeast from scratch could change industries around the world.

"This is a tour-de-force in synthetic biology," says James Collins, a biomedical engineer at Boston University, who is not involved in the project. He says the Synthetic Yeast 2.0 project "highlights our ever-expanding ability to modify and engineer DNA."

Tinkering With Chromosomes

While there have been experiments to make entire synthetic life forms—including a 2010 project that replaced a bacteria's DNA with a man-made carbon copy—Boeke's project differs in two key ways. First, a bacteria has much smaller genome in a simple loop of DNA, while the much more complex yeast has distinct chromosomes. And unlike any previous experiment, Boeke and his colleagues are making significant changes to their organism's DNA.

The chromosomes, designed by undergraduates in a 'Build-A-Genome' course at Johns Hopkins, are trimmed versions of the natural ones, with a few additional changes. The researchers have cut what they believe are the redundant or unnecessary segments of code—so called 'junk-DNA'—that are byproducts of the chaotic process of evolution.

"So what we're doing is, in some sense, a risky business," Boeke says. "There's not a flag on each segment saying 'this one's not important'. It's really a judgment call at a certain stage." Luckily, yeasts, like fruit flies and mice, are one of the best-understood organisms in all biology, so the scientists relied on a huge genetic database to guide them. "But if we make a mistake, as we've found in some of our unpublished work, the penalty could be a dead yeast," he says. "So we were pretty conservative."

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The researchers found their snips to the third chromosome had no apparent impact on the livelihood of their microbe—it lives and breeds as any other yeast would. "But we can't completely predict the effect of all the changes we're making," Boeke says. For one thing, over the last few decades researchers have discovered that often what seems to be genetic junk is anything but. Lines of seemingly useless DNA can encode for important properties during periods of high stress—such as low temperature or food availability—and it's possible that the researchers could have accidentally deleted genes that are occasionally beneficial.

But for the geneticists, that's just fine. Any accidental deletion, or any change caused by their synthetic DNA, will help the researchers to understand how their code translates to their living organism. Boeke says that alone was his biggest impetus for this project—he sees his man-made yeast as a learning tool. However, this new technology has other researchers excited for different reasons.

The Beers of the Future?

The prospect of yeast-by-design is tantalizing for many researchers in industries, such as brewing and biofuel, that require yeasts for industrial purposes but are limited to the best that nature can offer.

"This could be absolutely groundbreaking," says Chris Baugh, a former brewer and current research scientist at Sierra Nevada Brewing Company. "I'm personally more excited about these [synthetic] yeasts than any other scientific advancement I see coming into the brewing industry."

Baugh is speaking for himself here, he insists, and not for Sierra Nevada. Like many breweries, it sets its brewing standards based on traditional methods such as using only whole cone hops, and Baugh admits that any sort of modified yeast goes against that philosophy. But as a beer researcher, he's got plenty of reason to get excited.

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"It depends on what style of beer you're brewing, but I would say the yeast is responsible for at least half that flavor, though less so in beers like IPAs where the yeast's flavor can be overpowered by hops," he says. "Right now, the issue brewers face is that a lot of yeasts will produce these amazing flavors, but they may not ferment right"—for example, they'll produce too low of an alcohol level, he says. "But if you could tailor-make your yeasts, with the understanding of what genes code for the different flavor molecules, well, that opens the doors to the mass production of beer with totally untasted characteristics."

Because the public has been wary of GMO foods, Baugh says we'll probably see synthetic yeasts in biofuels long before we see them in the beers of the future. "The corn ethanol industry will be very excited about this. Their entire feedstock is already GMO, so there's no concern about using GMO yeasts." The science is here, Baugh says, and Synthetic Yeast 2.0 is proof. "There's nothing stopping this technology from advancing—the question is which industries are going to step forward and accept it."

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